| 1. |
- Björkenstam, Emma, et al.
(författare)
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Mental disorders and suicidal behavior in refugees and Swedish-born individuals : is the association affected by work disability?
- 2020
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Nature. - 0933-7954 .- 1433-9285. ; 55:8, s. 1061-1071
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAmong potential pathways to suicidal behavior in individuals with mental disorders (MD), work disability (WD) may play an important role. We examined the role of WD in the relationship between MD and suicidal behavior in Swedish-born individuals and refugees.MethodsThe study cohort consisted of 4,195,058 individuals aged 16–64, residing in Sweden in 2004–2005, whereof 163,160 refugees were followed during 2006–2013 with respect to suicidal behavior. Risk estimates were calculated as hazard ratios (HR) with 95% confidence intervals (CI). The reference groups comprised individuals with neither MD nor WD. WD factors (sickness absence (SA) and disability pension (DP)) were explored as potential modifiers and mediators.ResultsIn both Swedish-born and refugees, SA and DP were associated with an elevated risk of suicide attempt regardless of MD. In refugees, HRs for suicide attempt in long-term SA ranged from 2.96 (95% CI: 2.14–4.09) (no MD) to 6.23 (95% CI: 3.21–12.08) (MD). Similar associations were observed in Swedish-born. Elevated suicide attempt risks were also observed in DP. In Swedish-born individuals, there was a synergy effect between MD, and SA and DP regarding suicidal behavior. Both SA and DP were found to mediate the studied associations in Swedish-born, but not in refugees.ConclusionThere is an effect modification and a mediating effect between mental disorders and WD for subsequent suicidal behavior in Swedish-born individuals. Also for refugees without MD, WD is a risk factor for subsequent suicidal behavior. Particularly for Swedish-born individuals with MD, information on WD is vital in a clinical suicide risk assessment.
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| 2. |
- Clark, Alice, et al.
(författare)
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Sleep Impairment and Prognosis of Acute Myocardial Infarction : A Prospective Cohort Study
- 2014
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 37:5, s. 851-U215
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI). Design: Prospective cohort study. Setting: The Stockholm Heart Epidemiology Program, Sweden. Participants: There were 2,246 first-time AMI cases. Measurements and Results: Sleep impairment was assessed by the Karolina Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95-3.00), stroke (HR = 2.61; 95% CI: 1.19-5.76), and heart failure (HR = 2.43; 95% CI: 1.18-4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76-6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis. Conclusion: Results suggest sex-specific effects of impaired sleep that differ by short-and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention.
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| 3. |
- Clark, Alice, et al.
(författare)
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Workplace discrimination as risk factor for long-term sickness absence : Longitudinal analyses of onset and changes in workplace adversity
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- Workplace discrimination may affect the health of the exposed employees, but it is not known whether workplace discrimination is also associated with an increased risk of long-term sickness absence. The aim of this study was to examine the longitudinal associations of changes in and onset of workplace discrimination with the risk of long-term sickness absence. Data on workplace discrimination were obtained from 29,597 employees participating in survey waves 2004, 2006, 2008 and/or 2010 of the Finnish Public Sector Study. Four-year changes in long-term sickness absence (>= 10 days of medically certified absence with a mental or non-mental diagnosis) were assessed. This covered successive study waves in analyses of onset of workplace discrimination as well as fixed effect analyses of change in workplace discrimination (concurrent i.e. during the exposure year and 1-year lagged i.e. within one year following exposure), by using each employee as his/her own control. The risk of long-term sickness absence due to mental disorders was greater for employees with vs. without onset of workplace discrimination throughout the 4-year period, reaching a peak at the year when the onset of discrimination was reported (adjusted risk ratio 2.13; 95% confidence interval (CI) 1.80-2.52). The fixed effects analyses showed that workplace discrimination was associated with higher odds of concurrent, but not 1-year lagged, long-term sickness absence due to mental disorders (adjusted odds ratio 1.61; 95% CI 1.33-1.96 and adjusted odds ratio 1.02; 95% CI 0.83-1.25, respectively). Long-term sickness absence due to non-mental conditions was not associated with workplace discrimination. In conclusion, these findings suggest that workplace discrimination is associated with an elevated risk of long-term sickness absence due to mental disorders. Supporting an acute effect, the excess risk was confined to the year when workplace discrimination occurred.
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| 4. |
- Granholm, Anders, et al.
(författare)
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Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
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| 5. |
- Granholm, Anders, et al.
(författare)
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Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial : Protocol
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
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| 6. |
- Granholm, Anders, et al.
(författare)
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Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
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| 7. |
- Granholm, Anders, et al.
(författare)
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Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
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| 8. |
- Grynderup, Matias Brødsgaard, et al.
(författare)
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The associations between workplace bullying, salivary cortisol, and long-term sickness absence : a longitudinal study
- 2017
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 17:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absence. The primary aim of this study was to investigate to what extent cortisol levels were associated with subsequent sickness absence and if cortisol mediated the association between workplace bullying and sickness absence. We additionally investigated possible bidirectional associations between bullying, cortisol, and long-term sickness absence.METHODS: Participants came from two Danish cohort studies, the "Psychosocial RIsk factors for Stress and MEntal disease" (PRISME) cohort and the "Workplace Bullying and Harassment" (WBH) cohort (n = 5418). Information about exposure to workplace bullying and morning and evening salivary cortisol was collected at three time points with approximately two years in between. After each data collection, all participants were followed for two years in registers, and cases with long-term sickness absence lasting 30 or more consecutive days were identified. The association between cortisol levels and subsequent sickness absence was assessed by logistic regression, while the extent to which the association between bullying and sickness absence was mediated by cortisol was quantified through natural direct and indirect effects.RESULTS: High evening cortisol was associated with a decreased risk of sickness absence (OR = 0.82, 95% CI = 0.68-0.99), but we did not find that high morning cortisol levels (OR = 0.98, 95% CI = 0.81-1.18) or high morning-to-evening slope (OR = 0.99, 95% CI = 0.82-1.18) were associated with subsequent sickness absence. We also tested for reverse causation and found that long-term sickness absence, but not salivary cortisol, was a strong risk factor for subsequent workplace bullying. There was no indication that cortisol mediated the association between workplace bullying and sickness absence.CONCLUSION: We found no straightforward and simple association between cortisol and long-term sickness absence. Furthermore, the association between workplace bullying and long-term sickness absence was not mediated by cortisol.
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| 9. |
- Hulvej Rod, Naja, et al.
(författare)
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Sleep Disturbances and Cause-Specific Mortality : Results From the GAZEL Cohort Study
- 2011
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 173:3, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Poor sleep is an increasing problem in modern society, but most previous studies on the association between sleep and mortality rates have addressed only duration, not quality, of sleep. The authors prospectively examined the effects of sleep disturbances on mortality rates and on important risk factors for mortality, such as body mass index, hypertension, and diabetes. A total of 16,989 participants in the GAZEL cohort study were asked validated questions on sleep disturbances in 1990 and were followed up until 2009, with <1% loss to follow-up. Body mass index, hypertension, and diabetes were measured annually through self-reporting. During follow-up, a total of 1,045 men and women died. Sleep disturbances were associated with a higher overall mortality risk in men (P = 0.005) but not in women (P = 0.33). This effect was most pronounced for men <45 years of age (≥3 symptoms vs. none: hazard ratio = 2.03, 95% confidence interval: 1.24, 3.33). There were no clear associations between sleep disturbances and cardiovascular mortality rates, although men and women with sleep disturbances were more likely to develop hypertension and diabetes (P < 0.001). Compared with people with no sleep disturbances, men who reported ≥3 types of sleep disturbance had an almost 5 times' higher risk of committing suicide (hazard ratio = 4.99, 95% confidence interval: 1.59, 15.7). Future strategies to prevent premature deaths may benefit from assessment of sleep disturbances, especially in younger individuals.
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| 10. |
- Jakobsen, Janus Christian, et al.
(författare)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥37.8°C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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